Child abuse occurs at epidemic rates, with victims of abuse comprising a significant proportion of all child psychiatric admissions. While not all abused children develop difficulties, many experience a chronic course of psychopathology, with depression 1 of the most common psychiatric sequelae reported in maltreated children. This application outlines plans to examine genetic and environmental modifiers of depression in maltreated children. The hypotheses proposed in this grant are derived from recent advances in research on the neurobiology of stress and emerging understandings of the role of neuroplasticity in the pathophysiology and treatment of depression. 400 7-12 year old children will be recruited for this study: 200 maltreated children and 200 demographically-matched comparison children with no history of maltreatment or exposure to domestic violence. Detailed assessments of psychiatric symptomatology, trauma, life stressors, and social supports will be obtained, and serotonin transporter (5-HTTLPR) and brain derived neurotrophic factor (BDNF) genotyping will be completed from buccal cell DNA specimens. The primary aims of this investigation are to: 1) Examine 5-HTTLPR x BDNF interactions in the development of depression following stress;and 2) Examine the potential additional modifying effect of social supports on the development of depression. Exploratory analyses will also be conducted to examine the impact of genetic and environmental factors on 3 well-characterized depression endophenotypes. 2 of the endophenotypes have been widely used in cognitive neuroscience research, and the brain systems that mediate performance on these tasks are implicated in the neurobiology of depression. The results of this investigation will provide novel data on gene x gene and gene x environment interactions, and will lay the groundwork for future gene x gene and gene x environment studies of the neural circuits involved in the pathophysiology of depression. In addition, the findings will suggest multiple levels of targets for future intervention efforts in the treatment of stress-induced depression.